From the Editor
Gene Therapy: In Search of Silver Linings
Dr Rounak Dubey, MD
Junior Associate Editor, ISCT Telegraft
Assistant Professor Transfusion Medicine
NRI Academy of Medical Sciences, India
“You can’t connect the dots looking forward; you can only connect them looking backwards.”
- Steve Jobs
The evolving gene therapy approaches for Transfusion-Dependent Thalassemia (TDT) and Sickle Cell Disease (SCD) have the potential to impact lives on a global scale. Around 1.5% of the world population is estimated to be carriers of beta-thalassemia, and 60,000 symptomatic individuals are born annually . A majority of them belong to low/middle-income countries and gene therapy seems beyond their reach in the near future, especially after failed attempts to commercialize betibeglogene autotemcel (Zynteglo) in the European Union . What appears to be a setback at present may turn out to be the impetus for economies of scale in retrospection. Counting on the momentum gained in the last decade, we can still be cautiously optimistic that it will not remain a mere utopian dream and will translate into an affordable reality eventually.
In the previous edition of the Telegraft, the President’s desk article emphasized how regional developments in the field will guide the way forward. In a review article published by ISCT Stem Cell Engineering Committee, it was recommended that gene therapy may ultimately be more workable for developing countries provided the follow-up care is minimal. The paper also suggested a model where patients may be treated in a centralized center but return to a local center for monitoring . In this context, geographical regions with a high prevalence of TDT (Middle East, Southeast Asia and the Mediterranean basin) need special consideration. Preliminary results from China using CRISPR-Cas9-mediated gene editing of the BCL11A, carried out on 2 TDT patients, appear promising after 2 years of follow-up . India has the largest number of children with Thalassemia major in the world, around 1.5 lakhs (100,000), as per the report published by National Health Mission . There is no ongoing gene therapy trial for TDT in India at present. Dr Sudheendra Rao N R, (Scientific Advisor, Organization for Rare Diseases India) is of the opinion that “Given the growth in biosimilar industry in India and ongoing CAR-T trials, one can expect attempts of indigenous gene therapy products in this decade.”
The perception and expectations of the patients are pivotal in shaping the future ahead. In a survey conducted of TDT patients and their parents (Atlanta, US) the end result of therapy to be reduced blood transfusion and chelation was also acceptable to a majority of the participants . Healthcare Costs at 100-Day Follow-Up for those having a Pediatric Allogenic transplant, is around 585,300 USD in the US. While the cost for a similar procedure in a low/middle income country like India is approximately around 25,000 USD. Indian firms, like ImmunoACT are already in the process of launching indigenously developed CAR-T therapies in the range of 25,000 to 40,000 USD by 2024. All these developments have already laid down the basic foundation for advancing the steps ahead.
More data from ongoing clinical trials and long-term follow-up reports will lead to the development of better vectors, refined process controls and eventually a better supportive worldwide ecosystem. These hemoglobinopathies are often considered to be the “curse” of civilization, which originated initially as a protective mechanism. Perhaps the time is not very far, when this curse will be lifted once and for all.
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- Leonard A, Bertaina A, Bonfim C, et al. Curative therapy for hemoglobinopathies: an International Society for Cell & Gene Therapy Stem Cell Engineering Committee review
- Fu, Bin et al. “CRISPR-Cas9-mediated gene editing of the BCL11A enhancer for pediatric β0/β0 transfusion-dependent β-thalassemia.” Nature medicine vol. 28,8 (2022): 1573-1580.
- Quarmyne, MO., Ross, D., Sinha, C. et al. Decision-making about gene therapy in transfusion dependent thalassemia. BMC Pediatr 22, 536 (2022).